Full Project 2: Improving Testing, Triage, and Followup for Cervical Cancer Screening in Medically Underserved Women

摘要 这种NCCU-ESTA合作旨在评估新的方法，以减少差距和发病率 高级别癌前病变（CIN2+）和浸润性宫颈癌的死亡率（1） 通过检测尿液样本，而不是医生收集的样本， （2）增加对异常筛查结果随访的依从性，（3）减少不必要的 对检查结果异常的妇女进行后续检查。我们将评估这些方法， 完成以下具体目标： 目的1：评估尿液中致癌性人乳头瘤病毒（HPV）检测的有效性， 医生采集的宫颈样本，用于检测高度宫颈上皮内瘤变（CIN2+）。 我们会：（1）为160名参加该计划的病人进行尿液及子宫颈样本的人类乳头瘤病毒测试 阴道镜检查诊所和250名在宫颈癌初筛时细胞学正常/HPV阳性结果的女性 （2）计算有效性（敏感性、特异性、阳性率）， 和阴性预测值）的新的尿液诊断测试检测活检证实的CIN-2+。 目的2：研究新的方法来提高患者对后续阴道镜筛查的依从性-需要 适当转诊治疗和预防侵袭性癌症-通过（a）评估 尿HPV检测与基于临床的Pap或HPV/Pap联合检测，以及（B）开发内容和方案 以短信为基础的干预措施，以增加阴道镜检查的出勤率，将在未来的疗效试验中进行测试。 2a.我们将对15名接受宫颈癌筛查的妇女进行半结构式访谈， 他们对HPV尿液检测的理解和态度与诊所内Pap/HPV联合检测相比。 2b：我们将对出现异常阴道镜检查的女性进行目标受众评估。 筛选结果，然后使用此评估和现有的证据来制定和试点测试的内容， 建议量身定制的短信提醒干预，旨在改善患者对阴道镜检查的随访。 目的3：研究HPV 16型和18型E6蛋白检测在宫颈癌中的临床应用价值。 在HPV阳性妇女中检测CIN-2+，以评估其在阴道镜检查分诊中的应用潜力。 我们将（1）完成对目标1中从以下患者采集的尿液和宫颈样本的HPV E6检测： 细胞学阴性/HPV阳性筛查结果：初筛患者250例，阴道镜检查患者40例; (2)计算活检证实的有效性（灵敏度、特异性、阳性和阴性预测值） HPV E6分流检测CIN-2+在细胞学正常的HPV阳性女性中的应用 该项目的成功完成将为改进和改进环境管理的新方法提供有价值的见解。 有效性和减少宫颈癌筛查的资源负担，以及开展研究 NCCU合作者的技能，并为未来成功进行更大规模试验的建议提供基础。

Abstract This NCCU-UNC collaboration seeks to evaluate novel approaches to reduce disparities in and the morbidity and mortality attributable to high-grade precancerous lesions (CIN2+) and invasive cervical cancer by (1) improving the accessibility of primary screening by testing urine samples rather than physician-collected samples, (2) increasing adherence to follow-up of abnormal screening results, and (3) reducing unnecessary referral to follow-up screening among women with abnormal results. We will evaluate these approaches by completing the following specific aims: Aim 1: Assess the validity of testing for oncogenic human papillomavirus (HPV) in urine compared to physician-collected cervical samples for the detection of high-grade cervical intra-epithelial neoplasia (CIN2+). We will: (1) Conduct HPV testing in urine and cervical samples from 160 patients attending the UNC colposcopy clinic and from 250 women with cytology normal/ HPV positive results at UNC primary screening clinics, followed by colposcopy with directed biopsy, (2) Calculate the validity (sensitivity, specificity, positive and negative predictive values) of the new urine diagnostic test for detection of biopsy-confirmed CIN-2+. Aim 2: Examine new approaches to improve patient adherence to follow-up colposcopy screening – needed for the appropriate referral to treatment and prevention of invasive cancer – by (a) assessing perceptions of urine HPV-testing versus clinic-based Pap or HPV/Pap co-testing, and (b) developing the content and protocol for a text-message-based intervention to increase colposcopy attendance, to be tested in a future efficacy trial. 2a. We will conduct semi-structured interviews with 15 women undergoing cervical cancer screening to assess their understanding of and attitudes towards HPV urine testing compared to in-clinic Pap/HPV co-testing. 2b: We will conduct a target audience assessment of women referred to colposcopy following an abnormal screening result, then use this assessment and existing evidence to develop and pilot test the content of a proposed tailored text-message reminder intervention designed to improve patient follow-up to colposcopy. Aim 3: Investigate the clinical performance of testing for the E6 protein of HPV types 16 and 18 for the detection of CIN-2+ among HPV-positive women in order to assess its potential for use in triage to colposcopy. We will (1) Complete HPV E6 test testing on urine and cervical samples collected in Aim 1 from patients with cytology negative/HPV-positive screening results: 250 primary screening patients and 40 colposcopy patients; (2) Calculate the validity (sensitivity, specificity, positive and negative predictive values) for biopsy-confirmed CIN-2+ of HPV E6 triage testing among HPV-positive women with normal cytology. The successful completion of this project will provide valuable insight into new approaches to improve effectiveness and reduce the resource burden of cervical cancer screening, as well as develop the research skills of the NCCU collaborators and provide a basis for future successful proposals to conduct larger trials.